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ObjectiveTo explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.MethodsIt was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.ResultsAmong 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P < 0.001).ConclusionDynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.

Hydroprocessing technology is critical to reducing the sulfur and nitrogen content of complex heavy petroleum fractions, including vacuum gas oil (VGO) to increase the product value, to meet EPA regulations, and to avoid hampering the downstream processing. The catalyst design for hydroprocessing of VGO is of key importance, as the catalyst must perform multiple tasks in a complex and corrosive mixture. In this work, a combined approach is discussed that involves testing state-of-the-art catalysts for hydrodenitrogenation (HDN) and characterizing real VGO samples before and after HDN, using the advanced characterization method of ion mobility–mass spectrometry (IMMS). While other solvent systems have been reported, it is found that dichloromethane with 0.05% (v/v) trifluoroacetic acid is efficient for ionizing carbazole-type species, in addition to other nitrogen species. Comparing samples from three different catalysts reveal that catalysts A, B, and C can achieve similar performance for deep HDN. Intere...

Additional file 9. Review history.

Additional file 5. Clinical characteristics of all samples in the study.

Additional file 6. Oligonucleotides for PCR, RNA interference and sgRNAs.

Additional file 1. Figure S1. Identification of LAMP5-AS1 transcripts. a Agarose gel for the 5’ and 3’ RACE identified LAMP5-AS1 transcripts in THP1 cells. Two 5’-ends and one 3’-end of LAMP5-AS1 variant cDNA in cells were identified by the nested PCR. Schematic depiction of the two LAMP5-AS1 transcripts (bottom). b qRT-PCR for the relative expression of the two different LAMP5-AS1 transcripts. Figure S2. Impact of LAMP5-AS1 on primary MLL leukemia differentiation. a LAMP5-AS1 was highly expressed in all MLL leukemia cell lines labeled by * (analyzed by △CT). b qRT-PCR analysis for LAMP5-AS1 knockdown in 4 primary cells from patients with MLL leukemia, including three ALL with MLL-AF9 and MLL-AF4 and an AML with MLL-AF10, respectively, after transduction with LAMP5-AS1 siRNAs or control. Error bars reflect ± SEM (*, p < 0.05, **, p < 0.01) in three independent experiments. c Representative graph for the flow cytometric analysis of the CD19+, CD11b+, or CD14+ cell populations in the primary MLL leukemia cells. d Representative graph for the flow cytometric analysis of the CD34+ cell populations in primary MLL leukemia cells. Histogram plots show the statistical values. Error bars reflect ± SEM (*, p < 0.05, **, p < 0.01) in three independent experiments. Figure S3. LAMP5-AS1 plays a role in MLL leukemia cell maintenance. a, b qRT-PCR analysis for LAMP5-AS1 knockdown in MLL leukemia cells, after transduction with LAMP5-AS1 siRNAs or control (a) and LAMP5-AS1 shRNAs or control (b). Error bars reflect ± SEM (**, p < 0.01; ***, p < 0.001) in three independent experiments. c-e Representative flow cytometry graphs showing the CD14 (c), CD11b (d), and CD19 (e) cell populations in MLL leukemia cells treated with LAMP5-AS1 knockdown relative to those levels in control. The values were analyzed by Error bars reflect ± SEM (*,p < 0.05, **,p < 0.01,***, p < 0.001) in three independent experiments. f Morphology of colonies of MLL leukemia cells 10 days upon shRNA-mediated knockdown of LAMP5-AS1. Scale bars, 100 μm. Error bars reflect ± SEM (***, p < 0.001) in three independent experiments. Figure S4. Identification of LAMP5-AS1 binding to DOT1L in cell nucleus. a We fractionated the nucleus and cytoplasm from the THP1 cells and found that LAMP5-AS1 predominantly localizes to the cell nucleus, with NEAT1 as a nuclear marker and hY1 as a cytoplasmic marker. Error bars reflect ± SEM (***, p < 0.001) in three independent experiments. b RNA FISH showing most of LAMP5-AS1 localizes in the nuclei of MLL leukemia cells. Scale bars, 5 μm. c Agarose gel showing the templates of LAMP5-AS1 and LAMP5-AS1 antisense in the RNA-pull-down assay. d Agarose gel showing the PCR template of DOT1L. e Western blotting of DOT1L-N-FLAG in the products of RIP, with beta-tubulin as the negative control. Cell lysis harvested from the DOT1L-N-FLAG stably expressed THP1 cells. f RIP of DOT1L-FLAG in MOLM13 indicating that LAMP5-AS1 was significantly enriched compared with U6, actin, and GAPDH. g RNA FISH and IF experiments showed that LAMP5-AS1 co-localizes with DOT1L in the nuclei of MV4-11 cells. Scale bars, 5 μm. h Agarose formaldehyde gel showing the in vitro RNA transcription of LAMP5-AS1 sections. Biotin labeled UTP was added in the reaction. Figure S5. Epigenomic changes upon LAMP5-AS1 knockdown. a ChIP-seq profiles of H3K79me2 and H3K79me3 at the CDK6 genomic loci in LAMP5-AS1-knockdown (green) compared with control (gray) MOLM13 cells. The y-axis scales represent read density per million sequenced reads. b H3K79me2(left) and H3K79me3(right) ChIP-qPCR for the core target genes of MLL fusion protein in the LAMP5-AS1 knockdown (red) compared with control (gray) established MOLM13 cells. Error bars reflect ± SEM (*, p < 0.05) from three independent experiments. c Representative meta-analysis plot showing H3K79me2 profile across the +10 kb to -10 kb genomic region around the TSS of MLL-AF9 target genes. Profiles of LAMP5-AS1-knockdown (green) compared with control (blue) MOLM13 cells are presented. Figure S6. Genomic changes upon LAMP5-AS1 knockdown or overexpression. a qRT-PCR analysis determined that the expression levels of the MLL fusion protein target genes including HOXA9, HOXA10 and MEIS1 were decreased upon LAMP5-AS1 knockdown in MV4-11 cells. Error bars reflect ± SEM (*, p < 0.05, **, p < 0.01; ***, p < 0.001) in three independent experiments. b qRT-PCR analysis determined that the expression levels of the MLL fusion protein target genes including HOXA9, HOXA10 and MEIS1 were decreased upon LAMP5-AS1 knockdown in 4 primary MLL leukemia cells. Error bars reflect ± SEM (*, p < 0.05, **, p < 0.01; ***, p < 0.001) in three independent experiments. c Western blotting for the protein levels of HOXA9 and Mesi1 in MLL leukemia cells transduced by LAMP5-AS1 siRNA and control. d Overexpression of LAMP5-AS1 transcript 1 in MLL leukemia cells (MOLM13, MV4-11, and THP1). e qRT-PCR analysis determined that the expression levels of the MLL fusion protein target genes including HOXA9, HOXA10 and MEIS1 were increased in MLL leukemia cell lines treated with LAMP5-AS1 overexpression. Error bars reflect ± SEM (*, p < 0.05, **, p < 0.01; ***, p < 0.001) in three independent experiments. f Immunoblot showing the protein levels of HOXA9 and Mesi1 upregulated upon overexpression of LAMP5-AS1 in MLL leukemia cell lines. Table S1. Patient demographics and clinicopathologic features. Table S2. Demographics and clinicopathologic features of primary MLL leukemia patient samples. Table S3. The primers used in this work. Table S4. siRNA/shRNA. Table S5. ALL of the antibodies and regents used in this study. Table S6. MS of proteins from LAMP5-AS1 pull down.

Additional file 7. Antibodies used in the research.

Additional file 2. Figure S1-S9(PDF) with figure legends.

Additional file 8. Complete western blot images of all figures in the manuscript.

Additional file 1: Figure S1. The association of circAF4 expression of the clinical pathological data characteristics and function in leukemia. Figure S2. CircAF4 regulates the MLL leukemia progression in vivo. Figure S3. CircAF4 regulates the MLL-AF4 expression by binding to miR-128-3p in a ceRNA manner.

Kinetic and isotopic data are used to interpret the mechanistic role of gaseous H2O molecules and of nonreducible (Al2O3) and reducible (TiO2 ,F e 2O3) supports on CO oxidation turnovers catalyzed by small Au clusters (

The thermal conductivity of evacuated packed powders of zeolite NaX have been measured as a function of particle size (2 μm and 800 nm) and temperature (ca. 5–390 K ). The temperature dependence of the thermal conductivity of polycrystalline zeolite NaX over the particle size range studied here is glass-like and the results show a clear particle size effect. Room temperature values of the effective thermal conductivity of NaX, adjusted to 100% packing fraction, are 0.16 and 0.08 W m −1 K −1 , for the 2 μm and 800 nm particle sizes, respectively.

The effects of channel structure and spatial constraints on n-hexane oxidation rates and regioselectivity were examined on Mn cations within channels of acidic zeolites. Active Mn cations were placed at exchange sites within channels in 8-membered (ZSM-58), 10-membered (ZSM-5 and ZSM-57), and 12-membered ring (MOR) channels by sublimation of MnI2. Synthesis rates for hexanols (ROH), hexanal/hexanones (R( H) O), and acids were proportional to hexylhydroperoxide (ROOH) concentrations on all Mn-zeolite catalysts, except Mn-ZSM-58, on which products formed exclusively via noncatalytic autoxidation because of restricted access to Mn cations present within small channels (0.36 nm). Catalytic decomposition of ROOH intermediates occurs on intrachannel Mn cations and is the kinetically relevant step in alkane oxidation. ROOH decomposition rate constants were 2.5, 1.4, and 0.41 mol (mol-Mn h)−1 (mM-ROOH)−1 on Mn-ZSM-5, Mn-ZSM-57, and Mn-MOR (403 K; 0.4 MPa O2), respectively. Regioselectivity was influenced by the constrained environment around Mn cations, which increased terminal selectivities above the values predicted from the relative bond energies of methyl and methylene C H bonds in n-hexane. Mn cations within 10-ring channels gave higher terminal selectivities (Mn-ZSM-5: 24%, k prim / k sec = 0.42 ; Mn-ZSM-57: 14%, k prim / k sec = 0.22 ) than those within 8-membered or 12-membered rings (Mn-MOR, Mn-ZSM-57: 8–10%, k prim / k sec = 0.12 – 0.14 ), because of restricted access in ZSM-58 and unconstrained transition states for C H bond activation in MOR. Terminal selectivities decreased with increasing alkane conversion, because unselective noncatalytic autoxidation pathways prevail as ROOH concentrations concurrently increase. ROOH intermediates can be scavenged from the extracrystalline liquid phase using H-zeolites with accessible protons, which inhibit unselective noncatalytic reactions and maintain higher terminal selectivities as conversion increases, albeit with a concomitant decrease in the rate of oxidation steps also involving ROOH intermediates.

The rate of n-hexane reactions with O2 increased in parallel with the concentration of hexyl hydroperoxide (ROOH) intermediates and with the number of Mnredox sites in microporous MnAPO-5 and MnAPO-18 catalysts. These data confirmed the catalytic nature of oxidation pathways and the mechanistic resemblance between n-alkane and cycloalkane oxidation pathways. Cyclohexane oxidation turnover rates were higher on MnAPO-5 than on MnAPO-18, because small channels in the latter inhibit contact between reactants and Mn active centers. In contrast, n-hexane oxidation turnover rates (per redox-active Mn center) were similar on MnAPO-5 and MnAPO-18, because smaller n-hexane reactants diffuse rapidly and contact active sites in both microporous structures. MnAPO-18 is able to select reactants based on their size, but no regiospecificity was detected on MnAPO-18 or MnAPO-5 for n-hexane oxidation to alkanols, aldehydes, and ketones (7−8% terminal selectivity). The relative reactivity of primary and secondary C−H bonds ...

Kinetic and isotopic measurements have led to a detailed description of the elementary steps required for cyclohexane (RH) reactions with O 2 on MnAPO-5 catalysts. Cyclohexyl hydroperoxide (ROOH) is an intermediate in cyclohexanol (ROH) and cyclohexanone [R( H) O] formation. Combined rates of ROH + R( H) O synthesis are first order in ROOH concentration and proportional to the number of redox-active framework Mn sites. Taken together with UV–visible evidence for Mn 2+ as the most abundant active structure during steady-state catalysis, these data indicate that ROOH decomposition on Mn 2+ is a kinetically relevant step. C 6 H 12 /C 6 D 12 kinetic isotope effects (KIE) for ROOH decomposition as a function of ROOH concentration are 2.5 at 403 K, consistent with O H bond cleavage at Mn 2+ O H in this elementary step. A catalytic ROOH decomposition cycle proceeding via adsorbed intermediates without the involvement of free radicals or their bimolecular termination accounts for measured alcohol/ketone product ratios. Mn 3+ species, initially present in air-treated MnAPO-5, activate R H bonds and lead to shorter initial induction periods for ROOH-mediated pathways. tert -Butyl hydroperoxide (TBHP) led to higher ROOH synthesis rates via H abstraction from RH to form ROOH, without influencing ROOH decomposition rate constants. In the absence of TBHP, ROOH formation occurs predominantly through activation of C H bonds in RH by ROO ∗ species in a step that gives a KIE value of 6.8, consistent with such activation steps. These findings are expected to be also relevant for related RH oxidation reactions on materials containing redox-active sites such as inorganic solids or solvated cations. The proposed sequence of elementary steps illustrates the difficulties in interpreting effects of isotopic identity on rates and of spatial constraints on regioselectivity without rigorous assessment of the identity and kinetic relevance of elementary steps, and also the risk of using overall KIE values as phenomenological inference for a certain mechanism, particularly for sequential pathways, such as the ROOH formation and ROOH decomposition steps discussed here.

New materials that contain both organic and inorganic components have potentially new chemical and physical properties that can even lie outside those bracketed by their constituents. A series of hybrid polymer-inorganic nanocomposite materials was synthesized using various poly(ethylene oxide), LiCF3SO3, and zeolite mixtures. The series included mixtures of SiO2, PEO-LiX, and PEO-GLYLiX, of varying concentrations (where GLY 1/4 3-glycidoxypropyltrimethoxysi-lane, LiX is lithiated faujasite zeolite, and the Li+ source was LiCF3SO3; for all the LiCF3SO3-containing samples, the PEO oxygen: lithium mole ratio was 12: 1). Their degrees of crystallinity and glass transition temperatures relative to pure semicrystal-line PEO were found to be reduced on the addition of the inorganic components.

We report the controlled growth of poly(ethylene glycol) methyl ether grafted polymethacrylate (PEGPMA) on nanosized zeolite external surfaces using the atom transfer radical polymerization (ATRP) ...

We report the synthesis, using an organic-template-free hydrothermal crystallization method, and catalysis of a new type of nanocomposite material, 1.3 nm-sized RuO2 particles confined in faujasite zeolite. The zeolite-confined RuO2 composites were fully characterized with X-ray powder diffraction, Ru K-edge X-ray absorption, and high-resolution transmission electron microscopy. XRD and X-ray fluorescence analysis indicate that the framework is faujasite zeolite with a Si:Al ratio of 1.25. Ru K-edge X-ray absorption near-edge structures indicate that the ruthenium species in the zeolite is Ru(IV) with nearest-neighbor octahedral environments similar to hydrous RuO2, i.e., distorted "RuO6". The k2-weighted extended X-ray absorption fine structure indicates that the Ru(IV) species anchored in the zeolite likely form amorphous RuO2 with a 2D-chain structure, in which RuO6 units are connected together by two shared oxygen atoms. TEM shows that the particle size of RuO2 encapsulated inside the supercages of FAU is about 1.3 nm. The RuO2–FAU composites display significant catalytic activity in the oxidation of cyclohexane with tBHP under mild (room temperature and 1 atm (1 atm [Formula: see text] 101.325 kPa)) conditions. The ketone and alcohol concentration can be as high as 0.26 mol L–1 in 5 h with 48% peroxide efficiency. The catalyst is stable and reusable. Possible oxidation mechanisms are also discussed.Key words: nanocomposite, ruthenium oxide, catalysis, oxidation, zeolite.

Nanometer-sized faujasite zeolite (nanoNaX), synthesized with an organic-additive-free approach, was modified with organic functional groups. Raman scattering and solid-state NMR techniques were employed to study the organic components on the zeolites, the structures of the zeolitic frameworks, and the connections between the organosilyl groups and zeolitic silanol groups. Aminopropylsilyl (APS) and vinylsilyl (VS) groups were covalently grafted to the zeolitic surfaces by directly reacting the nanozeolite with corresponding organosilanes. Although the acryloyl group cannot be introduced onto the zeolitic surface by directly reacting nanoNaX with acryloyl chloride, acrylation can be achieved with APS-modified nanozeolite. 29Si solid-state NMR studies clearly indicate the transformation of zeolitic silicate species from Q3 to Q4 with organosilyl modification. This shows that the connections between the organosilyl groups and the zeolitic silanol groups can be represented as RSi(OSizeolite)x. In the APS-nan...

The development of green, selective, and efficient catalysts, which can aerobically oxidize a variety of alcohols to their corresponding aldehydes and ketones, is of both economic and environmental significance. We report here the synthesis of a novel aerobic oxidation catalyst, a zeolite-confined nanometer-sized RuO(2) (RuO(2)-FAU), by a one-step hydrothermal method. Using the spatial constraints of the rigid zeolitic framework, we sucessfully incorporated RuO(2) nanoparticles (1.3 +/- 0.2 nm) into the supercages of faujasite zeolite. Ru K-edge X-ray absorption fine structure results indicate that the RuO(2) nanoclusters anchored in the zeolite are structurally similar to highly hydrous RuO(2); that is, there is a two-dimensional structure of independent chains, in which RuO(6) octahedra are connected together by two shared oxygen atoms. In our preliminary catalytic studies, we find that the RuO(2) nanoclusters exhibit extraordinarily high activity and selectivity in the aerobic oxidation of alcohols under mild conditions, for example, air and ambient pressure. The physically trapped RuO(2) nanoclusters cannot diffuse out of the relatively narrow channels/pores of the zeolite during the catalytic process, making the catalyst both stable and reusable.

We have successfully synthesized NaX zeolite crystals with controlled sizes from 20 nm to 0.8 μm, using a novel organic-additive-free approach. We show that the NaX crystal size depends on the silicate source and hydrothermal crystallization conditions, especially crystallization temperature and agitation. The physical properties of NaX-nano (20−100 nm) were characterized by X-ray diffraction, high-resolution scanning electron microscopy, FT-IR spectroscopy, 29Si solid-state NMR spectroscopy, and N2 adsorption. The results were compared with those for micrometer-sized NaX crystals, NaX-μ. As expected, the external surface area of NaX-nano was found to be significantly enhanced compared with that of NaX-μ. Porosity analysis indicates that NaX-nano has a broad distribution of mesopores from 2 to 20 nm, associated with interparticle voids. Both FT-IR and 29Si solid-state NMR spectra revealed the presence of Q3 silicon atoms in NaX-nano. All four Q3 species were assigned in the 29Si NMR spectra.

Ultra-fine NaX zeolite crystals of dimensions ca. 20–100 nm have been synthesized with a novel, efficient, organic-additive-free hydrothermal approach.

The development of green, selective, and efficient catalysts, which can aerobically oxidize a variety of alcohols to their corresponding aldehydes and ketones, is of both economic and environmental significance. We report here the synthesis of a novel aerobic oxidation catalyst, a zeolite-confined nanometer-sized RuO(2) (RuO(2)-FAU), by a one-step hydrothermal method. Using the spatial constraints of the rigid zeolitic framework, we sucessfully incorporated RuO(2) nanoparticles (1.3 +/- 0.2 nm) into the supercages of faujasite zeolite. Ru K-edge X-ray absorption fine structure results indicate that the RuO(2) nanoclusters anchored in the zeolite are structurally similar to highly hydrous RuO(2); that is, there is a two-dimensional structure of independent chains, in which RuO(6) octahedra are connected together by two shared oxygen atoms. In our preliminary catalytic studies, we find that the RuO(2) nanoclusters exhibit extraordinarily high activity and selectivity in the aerobic oxidation of alcohols under mild conditions, for example, air and ambient pressure. The physically trapped RuO(2) nanoclusters cannot diffuse out of the relatively narrow channels/pores of the zeolite during the catalytic process, making the catalyst both stable and reusable.

Ultra-fine NaX zeolite crystals of dimensions ca. 20–100 nm have been synthesized with a novel, efficient, organic-additive-free hydrothermal approach.